Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

doi:10.1016/j.cclet.2016.02.009

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Abstract In order to discover highly active ecdysone analogs, a series of new substituted pyrazole amide derivatives were obtained using structure-guided optimization method and further screened for their insecticidal activities, in the basis of the core structures of the two active compounds N-(3-methoxyphenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6e) and N-(4-(tert-butyl)phenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6i), previously presented by us. The chemical structures of the title compounds were identified by spectral analyses. The preliminary bioassay results indicated that one among the synthesized pyrazole derivatives, compound 34, endowed with good activity against Mythimna Separata at 10 mg/L, which was equal to that displayed by the positive control tebufenozide. In addition, examples of molecular docking and molecular dynamics studies demonstrated that 34 may be the potential inhibitor to EcR and its docking conformation was similar to that of tebufenozide. In addition, increasing the hydrophobic effect and considering the suitable bulk effect on pyrazole ring are beneficial to the inhibiting activity to EcR and activity in vivo.

Key words： Moulting hormone Pyrazole amide Bioactivity Molecular docking Molecular dynamics simulation, Insect growth regulators

Received: 25 December 2015 Published: 02 March 2016

Fund:This work was supported by the National Natural Science Foundation of China (No. 21272265) and the National High Technology Research and Development Program of China (No. 2011AA10A204).

Corresponding Authors: Li Zhang, Xin-Ling Yang E-mail: zhang_li@cau.edu.cn;yangxl@cau.edu.cn

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http://www.chinchemlett.com.cn/EN/10.1016/j.cclet.2016.02.009 OR http://www.chinchemlett.com.cn/EN/Y2016/V27/I04/566

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